Innocente Steven A, Lee Jonathan M
Hamilton Regional Cancer Centre, Hamilton, Ontario, Canada.
Biochem Biophys Res Commun. 2005 Apr 8;329(2):713-8. doi: 10.1016/j.bbrc.2005.02.028.
The p53 protein family, comprised of p53, p63, and p73, has an important role in controlling cell growth and differentiation. We have previously reported that p53 prevents G(2)/M transition by decreasing intracellular levels of both cyclin B1 mRNA and protein, and attenuating the activity of the cyclin B1 promoter. The ability of p53 to control mitotic initiation by regulating intracellular cyclin B1 levels suggests that a cyclin B1-dependent G(2) checkpoint has a role in preventing neoplastic transformation. There is high sequence similarity between p73 and p53, suggesting that the two may have similar ability to repress transcription. In this report, we find that expression of p73alpha and p73beta isoforms can decrease the levels of cyclin B1 mRNA and attenuate expression from the cyclin B1 promoter. This attenuation occurs in both p53-deficient and p53-containing cell lines and cannot be inhibited by a p53 variant deficient in repressing cyclin B1 promoter activity. p73-mediated attenuation of the cyclin B1 promoter is dependent on the presence of functional Sp1-binding sites and is independent of the NF-Y-binding sites. This suggests that p73 mediates transcriptional repression through the Sp1 transcription factor.
由p53、p63和p73组成的p53蛋白家族在控制细胞生长和分化方面发挥着重要作用。我们之前报道过，p53通过降低细胞周期蛋白B1 mRNA和蛋白的细胞内水平，并减弱细胞周期蛋白B1启动子的活性，来阻止G(2)/M期转换。p53通过调节细胞内细胞周期蛋白B1水平来控制有丝分裂起始的能力表明，依赖细胞周期蛋白B1的G(2)检查点在预防肿瘤转化中起作用。p73与p53之间存在高度的序列相似性，这表明两者可能具有相似的抑制转录的能力。在本报告中，我们发现p73α和p73β亚型的表达可降低细胞周期蛋白B1 mRNA的水平，并减弱细胞周期蛋白B1启动子的表达。这种减弱在p53缺陷型和含p53的细胞系中均会发生，并且不能被抑制细胞周期蛋白B1启动子活性的p53变体所抑制。p73介导的细胞周期蛋白B1启动子的减弱依赖于功能性Sp1结合位点的存在，且独立于NF-Y结合位点。这表明p73通过Sp1转录因子介导转录抑制。
